Tramadol, which has the chemical name (+/−)-trans-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol, is a centrally acting synthetic opioid analgesic that is effective for the management of moderate to severe pain. After oral administration, tramadol is rapidly absorbed and metabolized into the pharmacologically active metabolite mono-O-desmethyltramadol. Conventional release preparations in the form of capsules, drops and suppositories containing tramadol have been commercially available for many years for use in the treatment of moderate to severe pain.
The prior art addresses the titration dosage regimen for immediate release tramadol. For example, U.S. Pat. No. 6,339,105 discloses a dosage regimen for immediate release tramadol including about 25 mg on days 1 to 3; 50 mg on days 4 to 6; 75 mg on days 7 to 9; 100 mg on days 10 to 12; 150 mg on days 13 to 15 and 200 mg on days 16 to 28. Also disclosed therein is a dosage regimen for immediate release tramadol including 25 mg q.d. on days 1 to 3; 25 mg b.i.d. on days 4-6, 25 mg t.i.d. on days 7 to 9; 25 mg q.i.d. on days 10 to 12; and 50 mg t.i.d. on days 13 to 28. The dosing of a controlled release form is not addressed in U.S. Pat. No. 6,339,105.
Controlled release tramadol is known to elicit adverse effects, including nausea, vomiting, sleepiness, dizziness, itchiness, sedation, dry mouth, sweating and constipation.
Thus, a need exists for the development of an advantageous dosing regimen for a controlled release dosage form of tramadol. More specifically, there exists a need for a dosage regimen for a controlled release tramadol which significantly reduces the occurrence of and concomitant severity of adverse tramadol elicited side effects, and thus, reduces potential discontinuation by patients due to these effects and increases the number of patients who may successfully be treated.